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Recent advancements in the treatment of melanoma are encouraging, but there remains a need to identify additional therapeutic targets. We identify a role for microsomal glutathione transferase 1 (MGST1) in biosynthetic pathways for melanin and as a determinant of tumor progression. Knockdown (KD) of MGST1 depleted midline-localized, pigmented melanocytes in zebrafish embryos, while in both mouse and human melanoma cells, loss of MGST1 resulted in a catalytically dependent, quantitative, and linear depigmentation, associated with diminished conversion of L-dopa to dopachrome (eumelanin precursor). Melanin, especially eumelanin, has antioxidant properties, and MGST1 KD melanoma cells are under higher oxidative stress, with increased reactive oxygen species, decreased antioxidant capacities, reduced energy metabolism and ATP production, and lower proliferation rates in 3D culture. In mice, when compared to nontarget control, Mgst1 KD B16 cells had less melanin, more active CD8+ T cell infiltration, slower growing tumors, and enhanced animal survival. Thus, MGST1 is an integral enzyme in melanin synthesis and its inhibition adversely influences tumor growth. [ABSTRACT FROM AUTHOR]

This study prospectively investigates the association between immunoglobulin G (IgG) N-glycan traits and ischemic stroke (IS) risk. A nested case-control study was conducted in the China suboptimal health cohort study, which recruited 4,313 individuals in 2013–2014. Cases were identified as patients diagnosed with IS, and controls were 1:1 matched by age and sex with cases. IgG N-glycans in baseline plasma samples were analyzed. A total of 99 IS cases and 99 controls were included, and 24 directly measured glycan peaks (GPs) were separated from IgG N-glycans. In directly measured GPs, GP4, GP9, GP21, GP22, GP23, and GP24 were associated with the risk of IS in men after adjusting for age, waist and hip circumference, obesity, diabetes, hypertension, and dyslipidemia. Derived glycan traits representing decreased galactosylation and sialylation were associated with IS in men (FBG2S2/(FBG2 + FBG2S1 + FBG2S2): odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87–0.97; G1n: OR = 0.74, 95% CI : 0.63–0.87; G0n: OR = 1.12, 95% CI : 1.03–1.22). However, these associations were not found among women. This study validated that altered IgG N-glycan traits were associated with incident IS in men, suggesting that sex discrepancies might exist in these associations. [ABSTRACT FROM AUTHOR]

An unexpected strategy for [beta]-catenin-dependent regulation of cell-lineage determination based on interactions between [beta]-catenin and a specific homeodomain factor, Prop1, is presented. A novel transcriptional strategy that underlies [beta]-catenin control of cell-lineage determination in organogenesis is discovered during the study.

Wines from different regions have different qualities due to the impact of geographical location and climate. The sale of inferior wines seriously violates the fair-trade rights of consumers. This article provides an elemental analysis classification method for verifying the geographical origin of wines in the People’s Republic of China. Inductively coupled plasma mass spectrometry, liquid chromatography isotope ratio mass spectrometry, and an isotope ratio mass spectrometer were used to analyze 142 wine samples collected from Helan Mountain, Xinjiang, Yunchuanzang, the Yanhuai Valley, and the Hexi Corridor regions. The data included elemental profiles, carbon isotope ratios (δ13C), and oxygen isotope ratios (δ18O). The results of multivariate analysis revealed that the geographical origin of wine is closely related to variations in elemental profiles and isotope ratios. Introducing δ18O and the elements Li, Mn, Ag, In, Th, Ta, and Re into the discriminant model yielded correct classification rates of the linear discriminant model of 90.8% for the training set and 87.3% for the test set. [ABSTRACT FROM AUTHOR]

Parkinson disease autosomal recessive, early onset 7 (PARK7 or DJ-1) is involved in multiple physiological processes and exerts anti-apoptotic effects on multiple cell types. Increased intestinal epithelial cell (IEC) apoptosis and excessive activation of the p53 signaling pathway is a hallmark of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). However, whether DJ-1 plays a role in colitis is unclear. To determine whether DJ-1 deficiency is involved in the p53 activation that results in IEC apoptosis in colitis, here we performed immunostaining, real-time PCR, and immunoblotting analyses to assess DJ-1 expression in human UC and CD samples. In the inflamed intestines of individuals with IBD, DJ-1 expression was decreased and negatively correlated with p53 expression. DJ-1 deficiency significantly aggravated colitis, evidenced by increased intestinal inflammation and exacerbated IEC apoptosis. Moreover, DJ-1 directly interacted with p53, and reduced DJ-1 levels increased p53 levels both in vivo and in vitro and were associated with decreased p53 degradation via the lysosomal pathway. We also induced experimental colitis with dextran sulfate sodium in mice and found that compared with DJ-1-/- mice, DJ-1-/-p53-/- mice have reduced apoptosis and inflammation and increased epithelial barrier integrity. Furthermore, pharmacological inhibition of p53 relieved inflammation in the DJ-1-/- mice. In conclusion, reduced DJ-1 expression promotes inflammation and IEC apoptosis via p53 in colitis, suggesting that the modulation of DJ-1 expression may be a potential therapeutic strategy for managing colitis. [ABSTRACT FROM AUTHOR]

Abstract In this work, carbon fiber needle-punching preforms were designed into two structure according to the density change along the thickness direction. One structure is designed to two layers with low-density layer and high-density layer, and the other is to three layers with low-density exterior layer and high-density interior layer. Then the effect of the preform with different structure on the densification rate and compressive properties of C/C composites was investigated. The results show that both two designed preforms can effectively avoid surface blocking, and lead to the faster densification rate of C/C composites during the chemical vapor infiltration processes. These results are attributable to the change of pore size distribution and pyrocarbon thickness, which was caused by fiber architecture designs. Meanwhile, these structural changes can improve the compressive strength of C/C composites, especially for the three-layer preforms. When the density of preforms is 0.45 g/cm3, C/C composites with three-layer preform has the highest compressive strength. The damage of most C/C composites with two and three-layer preforms is caused by shear or delamination failure, while that of C/C composites with common preforms usually caused by matrix collapse. Cracks in C/C composites with two and three-layer preforms always happened on the low-density layer, and consequently ceased or changed propagation direction in the interface between two layers. [ABSTRACT FROM AUTHOR]

Abstract Cabin thermal comfort is an important factor for the competitiveness of civil aviation. It has become a hot topic in recent years. However, there are still no clear standards for the thermal comfort in the aircraft cabin. In this paper, the cabin thermal comfort of passengers in 30 flights was investigated. Both objective and subjective data were collected in order to obtain a neutrality cabin temperature, T nc. The investigation shows that the distribution of Thermal Sensation Votes (TSVs) was approximately symmetric around the "Neutral" vote. The clothing insulation value of passengers, I CLO , was affected by the outdoor mean new effective temperature of departure city, ET*. T nc also changed with the outdoor ET*. According to this field surveys, a linear relationship is built between T nc and ET* as an adaptive model for the civil aircraft cabin. This adaptive model can be used as a reference to control the cabin operative temperature around the passengers. In this way, the cabin thermal comfort requirement may be satisfied for most of the passengers. Highlights • The thermal sensation votes were investigated onboard. • Subjective thermal sensation was obtained from the questionnaires. • A neutrality cabin temperature was built for the civil aircraft cabin. [ABSTRACT FROM AUTHOR]

This study provided phenotypic and molecular analysis of the antibiotic resistance within coagulase-negative staphylococci and lactic acid bacteria isolated from naturally fermented Chinese cured beef. A total of 49 strains were isolated by selective medium and identified at the species level by 16S rRNA gene sequencing as follows: Staphylococcus carnosus (37), Lactobacillus plantarum (6), Weissella confusa (4), Lactobacillus sakei (1), and Weissella cibaria (1). All strains were typed by random amplified polymorphic DNA fingerprinting, and their antibiotic resistances profiles to 15 antibiotics were determined as the MIC by using the agar dilution method. All the tested strains were sensitive to ampicillin, and most of them were also sensitive to penicillin, gentamycin, neomycin, norfloxacin, and ciprofloxacin with low MICs. High resistance to streptomycin, vancomycin, erythromycin, roxithromycin, lincomycin, and kanamycin was widely observed, while the resistant levels to tetracycline, oxytetracycline, and chloramphenicol varied. The presence of corresponding resistance genes in resistant isolates was investigated by PCR, with the following genes detected: tet(M) gene in 9 S. carnosus strains and 1 W. confusa strain; erm(F) gene in 10 S. carnosus strains; ere(A) gene in 6 S. carnosus strains; ere(A) gene in 4 S. carnosus strains and 1 L. plantarum strain; and str(A) gene and str(B) gene in 3 S. carnosus strains. The results indicated that multiple antibiotic resistances were common in coagulase-negative staphylococci and lactic acid bacteria strains isolated from naturally fermented Chinese cured beef. Safety analysis and risk assessment should be performed for application in meat products. [ABSTRACT FROM AUTHOR]

This paper aims to study the resistance of magnesium potassium phosphate cement (MKPC) paste to seawater erosion. MKPC paste specimens were prepared and their compressive strength, mass change, hydration temperature and water absorption were measured. The phase composition and microstructure were also analyzed. The results show that the initial hydration age of the reference sample M1 under natural curing condition has a significant effect on its compressive strength development in seawater. The residual ratios of the compressive strengths of M1(3d) and M1(28d), hydrated for 3 and 28 days, respectively, under natural curing condition, are 76.6% and 91.1% at 360-day seawater immersion age, respectively. This also indicates that early-age M1 has poor resistance to seawater erosion. Adding some limestone (LS) powders and silica fume (SF) can significantly improve the strength of early-age MKPC paste. The 3-day compressive strength of M2 with LS and SF is about 50% higher than that of M1. After immersion for 360 days in seawater, the residual ratios of the compressive strength of M2(3d) and M2(28d) are both close to 93%. This implies that initial hydration age of M2 under natural curing condition has almost no effect on its compressive strength development in seawater. Compared with M1, M2 has higher resistance to seawater erosion, which is attributed to the higher hydration degree and more compact structure of M2. This paper might be useful for preparing MKPC-based materials that can meet the requirements of marine concrete. [ABSTRACT FROM AUTHOR]

Meningioma is the most common primary intracranial tumor, but the molecular drivers of aggressive meningioma are incompletely understood. Using 280 human meningioma samples and RNA sequencing, immunohistochemistry, whole-exome sequencing, DNA methylation arrays, and targeted gene expression profiling, we comprehensively define the molecular profile of aggressive meningioma. Transcriptomic analyses identify FOXM1 as a key transcription factor for meningioma proliferation and a marker of poor clinical outcomes. Consistently, we discover genomic and epigenomic factors associated with FOXM1 activation in aggressive meningiomas. Finally, we define a FOXM1/Wnt signaling axis in meningioma that is associated with a mitotic gene expression program, poor clinical outcomes, and proliferation of primary meningioma cells. In summary, we find that multiple molecular mechanisms converge on a FOXM1/Wnt signaling axis in aggressive meningioma. [ABSTRACT FROM AUTHOR]

Glutathione S-transferase Pi (GSTP) is a thiolase that catalyzes the addition of glutathione (GSH) to receptive cysteines in target proteins, producing an S-glutathionylated residue. Accordingly, previous studies have reported that S-glutathionylation is constitutively decreased in cells from mice lacking GSTP (Gstp1/p2+/+). Here, we found that bone marrow-derived dendritic cells (BMDDCs) from Gstp1/p2-/- mice have proliferation rates that are greater than those in theirWTcounterparts (Gstp1/p2-/-). Moreover, Gstp1/p2-/- BMDDCs had increased reactive oxygen species (ROS) levels and decreased GSH:glutathione disulfide (GSSG) ratios. Estrogen receptor α (ERα) is linked to myeloproliferation and differentiation, and we observed that its steady-state levels are elevated in Gstp1/p2-/- BMDDCs, indicating a link betweenGSTPand ERα activities. BMDDCs differentiated by granulocyte-macrophage colony-stimulating factor had elevated ERα levels, which were more pronounced in Gstp1/p2-/- thanWTmice. When stimulated with lipopolysaccharide for maturation, Gstp1/p2-/- BMDDCs exhibited augmented endocytosis, maturation rate, cytokine secretion, and T-cell activation; heightened glucose uptake and glycolysis; increased Akt signaling (in the mTOR pathway); and decreased AMPK-mediated phosphorylation of proteins. Of note, GSTP formed a complex with ERα, stimulating ERα S-glutathionylation at cysteines 221, 245, 417, and 447; altering ERα's binding affinity for estradiol; and reducing overall binding potential (receptor density and affinity) 3-fold. Moreover, in Gstp1/p2-/- BMDDCs, ERα S-glutathionylation was constitutively decreased. Taken together, these findings suggest that GSTP-mediated S-glutathionylation of ERα controls BMDDC differentiation and affects metabolic function in dendritic cells. [ABSTRACT FROM AUTHOR]

Ground explosions are one of the threats to the structural integrities of buried pipelines. To investigate failure modes of buried pipelines subjected to ground explosions, numerical calculation models of buried pipelines in soil and rock layers were established. The stress, strain, plastic deformation and failure modes of the buried pipeline were investigated. The effects of the explosion magnitude, diameter-thickness ratio, burial depth, explosion height and explosion offset on the failure behaviour of the pipeline in the rock layer were studied. The results showed that the pipeline deformation process only lasted for 0.03 s. The high stress zone and plastic strain zone were present in the upper part of the pipeline, and a dent appears. A buried pipeline in a rock layer is more dangerous than that in a soil layer due to the reflection of the explosion wave in the rock layer. The deformation, plastic strain and total energy of the pipeline increase gradually in the rock layer with increasing explosion magnitudes or diameter-thickness ratios, but these indices decrease with the increased burial depths, explosion heights and explosion distances. Empirical formulas can be used to predict the strain and dent rates of the buried pipeline. These results can provide the theoretical basis and references for laying pipeline, as well as for their safety evaluations and maintenance, etc. [ABSTRACT FROM AUTHOR]

Drumstick is a tree with a range of potential commercial uses: the vegetative organs have high nutritional value and the seeds have high oil content. In the present study, an efficient regeneration protocol for this multipurpose tree has been developed using leaf segments as explants. In addition, the effects of genotype, developmental stage and inoculation orientation of the explants, and the combination of plant growth regulators (PGRs) in the culture medium have been investigated. It was found that Murashige and Skoog (MS) basal elements supplemented with 0.8 mg/L 6-benzyladenine (BA), 0.2 mg/L kinetin (KT) and 0.05 mg/L a-naphthaleneacetic acid (NAA) provided the most suitable medium for shoot-bud regeneration, delivering a maximum regeneration frequency of 93.33% and a mean of 4.40 shoots per explant. In addition, orienting the distal ends of the explants down towards the medium was much better than them facing upwards. We were able to root approximately 90% of the regenerated shoots on MS medium with 0.1 mg/L NAA. Even though success of this protocol varied according to genotype, it still has high applicability at a large scale and could be used in the production of high quality plantlets to meet large scale cultivation needs. In addition, it may be useful for genetic transformation studies. [ABSTRACT FROM AUTHOR]

The objective of this study is to investigate the effect of local wall thinning on the plastic limit load of modified 9Cr-1Mo steel pipe with existing creep damage based on the plastic limit load concept under high temperature. The creep damage is obtained from the Liu–Murakami creep model. A modified Ramberg–Osgood model is derived by using the relationship among the hardness, the creep damage, the yield strength and the ultimate tensile strength at high temperature to characterize the material deterioration during the creep process, where the non-uniform distribution of the material deterioration caused by the stress levels is considered. Orthogonal analysis for pipes with different type of defect under multi-loading systems are performed by using finite element method. The failure modes for pipes at limit state are revealed and the effect of local wall thinning on the plastic limit load of pipe with existing creep damage is presented. The regression formulae of the rupture time and the plastic limit load ratios for the pipes with different defect ratios and load combination ratios are established based on the numerical results. The limit loads for pipe with specified local wall thinning ratios after a period of time at high temperature can be determined conveniently through the regression formulae. [ABSTRACT FROM AUTHOR]

Our previous studies have demonstrated that KLF4 is a critical transcription factor that promotes the odontoblastic differentiation of dental papilla cells. Klf4 mRNA was found to be regulated by multiple microRNAs (miRNAs). Competitive endogenous RNAs (ceRNAs) are a group of transcripts post-transcriptionally regulating each other by competing for their common miRNAs. However, the regulation of Klf4 by ceRNAs in odontoblastic differentiation remains unknown. In this study, we predicted a group of potential Klf4 ceRNAs with bioinformatics approach, and examined the expression of Klf4 and five interested potential ceRNAs including Sp1 using real-time PCR during odontoblastic differentiation of mDPC6T. The expression levels of both Sp1 and Klf4 were significantly upregulated during this process. In situ hybridization verified that Sp1 was co-expressed with Klf4 in the differentiating and the mature odontoblasts in vivo. Knockdown of Sp1 using siRNA resulted in a significant reduction of Klf4 and vice visa. This interaction was further confirmed to be miRNA dependent. Common miRNAs of Klf4 and Sp1 were predicted, among which miR-7a, miR-29b and miR-135a were able to downregulate both Klf4 and Sp1 expression after their separate overexpression in the mDPC6T cells. Dual luciferase assays showed that these miRNAs separately regulated the 3'UTRs of both Klf4 and Sp1, and the down-regulation of Klf4 3 'UTR by Sp1 siRNA was abolished when these three miRNAs' binding sites were mutated in the Klf4 3 'UTR. Therefore, our results indicate that Sp1 functions as a ceRNA of Klf4 during odontoblastic differentiation through competing for miR-7a, miR-29b and miR-135a. [ABSTRACT FROM AUTHOR]

As Japan has announced its decision to start discharging radioactive water into the Pacific Ocean, it's expected that global marine environment pollution will worsen due to the contaminated water, posing a new challenge to the ballast water management system dominated by the flag state. In this context, this paper studies the equilibrium strategies on ship ballast water discharge controls between the flag states and the port states in different situations. Through a numerical study, we analyze how the ballast water discharge location, decision sequences of relevant states, the role of the International Environmental Protection Organization and its aid strategies impact the control strategies by the flag states and the port states. In the event of radioactive water discharge, the flag state controls alone do not yield satisfactory results, and the port state control is effective supplementation to the flag state control to mitigate risks of marine pollution. Furthermore, where the International Environmental Protection Organization takes reasonable aid steps, the flag states are incentivized to take control measures. [Display omitted] • The challenges of ship ballast water management will be much severer after nuclear water released by Japan. • Supplementary role of Port State Control to Flag State Control in ballast water management is discussed. • The role of International Environmental Protection Organization in ballast water management is discussed. • Policy suggestions are proposed for ballast water management under the background of nuclear water release. [ABSTRACT FROM AUTHOR]

This research aimed to estimate the effect of perceived social factors in the community stress and problems on the residents' psychopathology such as depression and suicidal behaviors. Subjects of this study were the informants (N = 1618) in a psychological autopsy (PA) study with a case-control design. We interviewed two informants (a family member and a close friend) for 392 suicides and 416 living controls, which came from 16 rural counties randomly selected from three provinces of China. Community stress and problems were measured by the WHO SUPRE-M1SS scale. Depression was measured by CES-D scale, and suicidal behavior was assessed by NCS-R scale. Multivariable liner and logistic regression models and the Structural Equation Modeling (SEM) were applied to probe the correlation of the depression and the suicidal behaviors with some major demographic variables as covariates. It was found that community stress and problems were directly associated with rural Chinese residents' depression (Path coefficient = 0.127, P< 0.001). There was no direct correlation between community stress and problem and suicidal behaviors, but community stress and problem can affect suicidal behaviors indirectly through depression. The path coefficient between depression and suicidal behaviors was 0.975. The current study predicts a new research viewpoint, that is, the depression is the intermediate between community stress and problem and suicidal behaviors. It might be an effective route to prevent depression directly and suicidal behaviors indirectly by reducing the community stress and problems. [ABSTRACT FROM AUTHOR]

Laser welding of highly reflective materials, such as copper, has suffered problems such as spatter, underfill and undercut for a long time. This work analyzed the associated mechanism and suggested that appearance and integrity of laser welded copper joint could be improved by conducting the welding process at a high welding speed which is slightly below the critical welding speed for full-penetration welding at the specified laser power. The microstructure, mechanical properties and electrical conductivity of the T2 copper joint achieved under high welding speed were tested. Results show that copper joint and base material (BM) have similar electrical conductivity, the weld fusion zone (FZ) and the heat affected zone (HAZ) are softened; the tensile strength and elongation of the joint are approximately 20% and 84% below those of the BM respectively. The joint breaks near the interface between the longitudinal columnar grain structures (LC) growing along welding direction at the FZ center, and the horizontal columnar grain structures (HC) growing perpendicular to the welding direction at other area of FZ. Degradation of the mechanical properties of copper joint is attributed to the softening of the heated zone and the big angle between the growth directions of LC and HC. [ABSTRACT FROM AUTHOR]

CP-Ti/X65-pipe-steel bimetallic sheet was fabricated by explosive welding and hot rolling (W&R). Trace of the wavy CP-Ti/X65 interface formed from explosive welding was observed along the straight CP-Ti/X65 interface of bimetallic sheet fabricated by W&R. The microstructure and component analysis showed the following. (i) The cross-section of the X65 zone consisted of a 2-5 µm-wide Ti diffusion layer next to the interface, a 150-200 µm-wide decarbonization layer, and the rest area with a banded structure morphology. (ii) There were numerous voids and a slight C element enrichment at the interface. (iii) The section of the CP-Ti zone consisted of a 10-50 µm-wide Fe diffusion zone next to the interface, a residual adiabatic shear band zone next to Fe diffusion zone, and the rest region composed of the a-Ti microstructure. The micro-hardness profile across CP-Ti/X65 interface was measured. The variation patterns of the mechanical properties of the bimetallic sheet in the thickness direction were obtained from stratified tensile tests. The shear test proved that the CP-Ti/X65 bimetallic sheet produced by W&R had acceptable shear bond strength. The microstructure and alloy element distribution across the TA1/X65 interfaces of as-welded, heat treated and extruded TA1/X65 bimetallic sheets were studied and compared. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess the association between single nucleotide polymorphisms in thrombospondin-1 (THBS1), thrombospondin-2 (THBS2), thrombospondin-4 (THBS4) and coronary artery disease (CAD) risk. Methods Electronic databases were searched before June, 2014 to obtain articles associated with thrombospondin polymorphisms and CAD risk. After identifying case-control studies, odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool effect sizes. Different effect models were used according to heterogeneity. Meta-regression and sensitivity analyses were performed to examine the heterogeneity source. Begg's funnel plot and Egger's test were conducted for publication bias. Results 13 studies involving 10,801 cases and 9,381 controls were included. Associations were observed between the THBS1 N700S polymorphism and CAD risk in general population(heterozygote model: OR = 1.14, 95% CI: 1.03-1.26; dominant model: OR = 1.13, 95% CI: 1.00-1.29), European population (heterozygote model: OR = 1.13, 95% CI: 1.00-1.27) and Asian population (heterozygote model: OR = 1.57, 95% CI: 1.01-2.44; dominant model: OR = 1.56, 95% CI: 1.00-2.43). The THBS2 3' untranslated region (UTR) polymorphism and THBS4 A387P polymorphism were not associated with overall CAD risk. However, an association was observed between the THBS4 A387P polymorphism and CAD risk in the American population (allele model: OR = 1.09, 95% CI: 1.00-1.18; homozygote model: OR = 1.29, 95% CI: 1.04-1.61; recessive model: OR = 1.27, 95% CI: 1.02-1.58). Conclusions The THBS1 N700S polymorphism was associated with increased CAD risk, especially in Asian and European populations. No association was observed between the THBS2 3' UTR polymorphism and CAD risk. The THBS4 A387P polymorphism was associated with increased CAD risk in the American population. [ABSTRACT FROM AUTHOR]